Italian researchers are exploring a novel approach to combatting hepatocellular carcinoma, the most common type of liver cancer, by disrupting the tumor’s blood supply. A study from the Ircss Saverio De Bellis institute indicates that combining the naturally occurring protein Proteoglycan-4 (PRG4) with the existing drug regorafenib substantially enhances the latter’s effectiveness [[3]]. This preclinical work,recently published in the *Journal of Experimental & Clinical Cancer Research*,suggests a potential pathway to improve treatment outcomes and reduce side effects for patients facing this aggressive cancer [[1]], [[2]].
A new strategy to limit the growth of liver cancer by cutting off its blood supply is showing promise, according to research from the Ircss Saverio De Bellis institute in Castellana Grotte, Italy. The approach, which “starves” the tumor of oxygen and nutrients, could offer a new avenue for treating this challenging disease, which affects thousands of people globally.
Researchers discovered that Proteoglycan-4 (PRG4), a glycoprotein naturally produced in joints and the surface of the eye but not in the liver, significantly enhances the effectiveness of regorafenib, a drug already used in liver cancer therapy. The study’s findings were published in the international journal Journal of Experimental & Clinical Cancer Research.
“Blocks Vessels and Deprives the Tumor of Supplies”
“The synergy between PRG4 and regorafenib prevents the formation of new blood vessels, limiting the supply of oxygen and nutrients and thus reducing the tumor’s ability to grow and spread,” explained Gianluigi Giannelli, scientific director of the De Bellis institute. The study, funded by the Italian Ministry of Health, was the result of over four years of scientific activity conducted on preclinical models created using molecular engineering techniques. Francesco Dituri was the lead author of the research.
The promising results have prompted the team to develop smaller fragments of PRG4, protected by an international patent and suitable for future clinical applications, Giannelli confirmed. A particularly relevant aspect of PRG4 is its immunological compatibility; as a naturally occurring molecule, it is not immunogenic, similar to insulin. This could make it a safer alternative to synthetic molecules.
Potential to Reduce Dosage and Side Effects
Researchers believe that combining PRG4 with regorafenib could potentially allow for a lower dosage of the drug, while maintaining or even increasing its effectiveness. This could also lead to a reduction in the side effects often associated with regorafenib, which can sometimes cause patients to discontinue treatment, and improve long-term tolerability. This represents a potential paradigm shift in the management of patients with liver cancer.
De Bellis Institute: A Leader in Patent Research
Enzo Delvecchio, president of the institute’s governing council, emphasized that the project confirms “the validity of the path undertaken by our Institute,” which is a leading center in Southern Italy for the national PerfeTTO project of the Ministry of Health, dedicated to the valorization of patent research.
Luigi Fruscio, the extraordinary commissioner, reiterated the central role of the De Bellis institute: “Research drives the improvement of care. It is not surprising that our researchers are conducting a national multicenter study on PRG4. Our Institute continues to be a center of excellence.”
